Effect of the disclosure of MS diagnosis on anxiety, mood and quality of life of patients: a prospective study.

BACKGROUND: In the light of the new diagnostic criteria for multiple sclerosis (MS) and currently available early treatment, this study aimed to explore whether, and to what extent, disclosure of the diagnosis of MS or clinically isolated syndrome (CIS) affects patients' anxiety, mood and quality of life (QoL). METHODS: Eligible participants were all patients referred for the first time to the Neurological Unit who had manifested symptoms suggestive of MS for no more than 6 months. All patients were evaluated for (i) QoL (SEIQoL and MS-QoL54), (ii) Anxiety (STAI) and Depression (CMDI) on study inclusion (T0), 30 days after diagnosis disclosure (T30), and after 1 (T1y) and 2 (T2y) years' follow-up. RESULTS: Two hundred and twenty-nine patients were enrolled; 93 of these were unaware of their diagnosis. Patients who already knew their diagnosis (100 with CIS and 22 with MS) were excluded from the main analyses and used to perform control analyses. At the end of the screening, an MS diagnosis was disclosed to 18 of the 93 patients, whereas a CIS diagnosis was disclosed to 62 patients (12 patients received a diagnosis other than MS or CIS). Thirty days after diagnosis disclosure, irrespective of the diagnosis disclosed, both QoL and Anxiety and Depression were significantly rated as better compared to the start of screening, (p(s) < 0.03), and this improvement remained stable over the two annual follow-ups. However, as suggested by a significant 'Time' × 'Diagnosis' interaction with regard to both QoL and Anxiety and Depression (p(s) < 0.02), the effect of the disclosure in the short term differed depending on CIS or MS diagnosis. Specifically, on MSQoL, which is a health-related QoL scale, we found a statically significant improvement, immediately after the diagnosis disclosure, in both the MS and CIS groups (p(s) < 0.01). Differently, on SEIQoL, which is a non health-related QoL measure, and on the anxiety scale, we observed a statistically significant improvement only in the group which received a MS diagnosis (p(s) < 0.03). CONCLUSIONS: This first prospective study provides objective data showing that early disclosure of MS diagnosis improves both the patient's QoL and psychological well-being. In addition, the results seem to suggest that CIS disclosure does not lead to the same favourable effects.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic-therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

Sleep--wake and body core temperature rhythms in multiple sclerosis with fatigue.

OBJECTIVE: To study sleep-wake and body core temperature (BCT) circadian rhythms in patients with multiple sclerosis (MS)-associated with chronic fatigue. METHODS: Six relapsing-remitting MS patients with chronic fatigue underwent 48 consecutive hours polysomnography (PSG) with BCT measurement, followed by a Multiple Sleep Latency Test (MSLT). All patients were relapse- and drug-free. Mood depression, brain and cervical cord enhanced MRI, dynamic spirometry and Fatigue Severity Scale (FSS) were assessed just before PSG. RESULTS: In all patients mood depression was absent and dynamic spirometry normal, but FSS confirmed fatigue. MRI showed non-enhancing lesions. Nocturnal sleep was characterized by normal architecture and mean sleep efficiency was only slightly reduced. Arousal index was normal and periodic limb movements during sleep (PLMS) were present in four patients, with an increased index (PLMS-I) in only two of them. Upon MSLT, mean sleep latency was normal in all patients with one sleep onset REM period in one patient. All patients displayed a normal BCT 24-h rhythm. Mesor, amplitude and acrophase of BCT rhythm did not show significant differences between MS and controls. CONCLUSIONS: We found substantially normal sleep-wake and BCT rhythmicity in six patients with MS and fatigue. Non-restorative sleep and abnormal BCT regulation were unlikely mechanisms of chronic fatigue in our MS patients. SIGNIFICANCE: Subjective fatigue and abnormal sleep and BCT can be independent manifestation in MS patients. The findings support the notion that objective measures of fatigue comparable to the MSLT for sleepiness do not exist.

A possible link between genetic hemochromatosis and autoimmune thyroiditis.

The systemic involvement that often characterizes genetic hemochromatosis is well known. Although evidence of iron storage in endocrine glands has been reported, the possible functional changes due to altered thyroid in course of hemochromatosis have been not clearly defined so far. Thyroid may be directly affected by iron storage in the gland as well as functionally altered due to iron accumulation occurring in the pituitary. The prevalence and the pathogenetic mechanisms of primary thyroid illness in patients with genetic hemochromatosis are still largely unknown. Hereby, we describe two patients affected by genetic hemochromatosis who developed Hashimoto's thyroiditis. Taking into consideration the possible links occurring among iron overload, thyroid gland damage and thyroid dysfunction, we hypothesize that hemochromatosis could have been an enhancing factor for the development of primary thyroid disease in these patients. Potentially, this process might also determine new onset anti-thyroid autoimmunity or overlap it. We conclude that systematic studies in large and heterogeneous populations will be necessary in order to assess the risk of development of primary thyroid disorders in course of genetic hemochromatosis and, more generally, chronic iron overload conditions. In our mind, thyroid function should be periodically checked in all patients with chronic iron overload conditions.

Effects of sodium DL-lactate on insulin secretion in anesthetized dogs.

The effect of sodium DL-lactate administration on insulin release in anesthetized dogs has been studied. Eleven mongrel dogs were infused with sodium DL-lactate for 20 min at the rate of 20 mg/kg . min. Lactate infusion produced simultaneous increases in blood glucose and plasma insulin levels in the pancreaticoduodenal vein. To determine whether lactate stimulated insulin secretion directly, sodium DL-lactate was rapidly injected into the pancreatic artery of six dogs; this pulse induced a significant increase in insulin release from pancreatic B-cells, even in the absence of a measurable change in blood glucose. Diazoxide, when infused in six dogs, blocked lactate-induced insulin secretion. These findings indicate that lactate, as do other circulating energy fuels, may play a role in the physiologic control of insulin secretion.

High incidence of sperm sex chromosomes aneuploidies in two patients with Klinefelter's syndrome.

In this study we have investigated the arrangement of sex chromosomes in sperm from two severe oligozoospermic patients, apparently affected by the classic form of Klinefelter's syndrome (KS). Multicolor fluorescence in situ hybridization has been used to recognize chromosomes X, Y, and 8 in sperm from patients and 10 fertile men with normal 46,XY karyotype. In patients affected by KS, we detected important numerical sex chromosome abnormalities (approximately 20%). In all normal fertile men, X- and Y-bearing spermatozoa were present in a 1:1 ratio. On the contrary, in our patients the frequency of 23,Y-bearing sperm was strongly reduced compared with that of both 23,Y sperm in the controls and 23,X sperm in the same subject affected by KS, resulting in a 23,X-/23,Y-bearing sperm ratio of 2:1. Moreover, the frequency of 24,XY disomic sperm was significantly higher in the absence of the 22,0 hypoaploidy expected from a common origin from a nondysjunction during the first meiosis in a normal 46,XY cell. In conclusion, the results of the present study demonstrate a peculiar distribution of sex chromosomes in sperm from two patients with KS, in agreement with the hypothesis that 47,XXY germ cells are able to complete the meiotic process by producing mature spermatozoa.

Plasma kallikrein activity in human diabetes mellitus.

It has recently been observed that administration of bradykinin to diabetic patients improves peripheral glucose utilization. To verify whether there is an alteration of the kallikrein-kinin system in human diabetes, plasma kallikrein activity was measured in 47 diabetic patients and in 20 control subjects. In diabetics plasma kallikrein activity was significantly higher than in controls: 1.04 +/- 0.04 U/ml (p less than 0.001). Although they do not refute the hypothesis that there is an alteration of the kallikrein-kinin system in diabetes mellitus, these findings do not support such a hypothesis either. Increased synthesis of plasma kallikrein activity may be due to increased synthesis of carbohydrate-protein compounds in diabetes mellitus.

Assessment of testicular cytology by fine needle aspiration as a diagnostic parameter in the evaluation of the azoospermic subject.

OBJECTIVE: To investigate whether testicular cytology by fine needle aspiration (FNA) may be considered a diagnostic parameter in the evaluation of the azoospermic subject. DESIGN: Cytologic smears were obtained using a 23-G needle, stained with May-Grünwald-Giemsa stain and examined under a light Orthoplan microscope (Wild, Leitz, Germany) for qualitative and quantitative analysis. PATIENTS: Fifty-four azoospermic patients were analyzed, and the findings were compared with those obtained from 40 normozoospermic infertile subjects used as controls. MAIN OUTCOME MEASURE(S): Two hundred spermatogenic cells were counted and classified at the various steps of spermatogenesis. Spermatic index and Sertoli index provided further elucidations and more comprehensible results. RESULTS: No sign of traumatization was observed. Cytologic analysis was proved to have high statistical reproducibility (P less than 0.01 for spermatogonia and secondary spermatocytes and P less than 0.001 for the other cell types, when compared between differential counts) and permitted identification of different situations associated with azoospermia: Sertoli cell-only syndrome, germ depopulation (hypospermatogenesis), spermatogonial arrest, spermatidic arrest, and obstructive azoospermia. These findings agreed with clinical and hormonal parameters and with the results of bilateral surgical biopsies, when performed. CONCLUSIONS: The results support use of FNA of the testis as a noninvasive diagnostic parameter for the assessment of azoospermic subjects.

Angiotensin-converting enzyme content of human spermatozoa and its release during capacitation.

In this study, we demonstrated, by using known detergents, the presence of angiotensin-converting enzyme (ACE) within human spermatozoa. We determined that maximal angiotensin-converting activity is expressed by sperm incubated in capacitating conditions, whereas this activity is negligible in saline-incubated spermatozoa. We further demonstrated that not acrosomes but cytoplasmic residues contain ACE. Because follicular fluid provides the necessary conditions for a maximal angiotensin-converting activity and for capacitations' metabolic activation, we hypothesize that ACE may play its physiologic role within the female reproductive tract.

Gonadal steroids and opioid control of gonadotropin secretion in man.

The aim of this study was to ascertain whether there was an interrelationship between gonadal steroids and endogenous opioid peptides. The effects of naloxone (20 mg, intravenously) and of a met-enkephalin analog (DAMME) (250 micrograms, intravenously) on gonadotropin secretion in three castrated men (18 to 23 years of age) and in five age-matched normal men were studied. Normal subjects were studied before and after treatment with a specific nonsteroidal estrogen receptor antagonist, clomiphene. Naloxone caused a significant increase in luteinizing hormone (LH) (P less than 0.05); in these subjects, clomiphene treatment significantly increased LH and follicle-stimulating hormone plasma levels but totally suppressed the naloxone-induced rise in LH. In castrated men, naloxone failed to increase plasma LH levels. However, DAMME significantly reduced plasma LH levels in normal, in castrated, and in clomiphene-treated normal subjects. The results demonstrate that in castrated subjects who lack gonadal steroids and in normal subjects with blocked estrogen receptors there is a reduced opioid inhibitory tone on gonadotropin secretion. The effect of DAMME on gonadotropin secretion, however, is not influenced by the gonadal steroid environment.

Serotonin but not dopamine is involved in the naloxone-induced luteinizing hormone release in man.

Endogenous opioid peptides exert a tonic inhibition on gonadotropin secretion at the hypothalamic level, but the mechanisms by which they act are still unknown. Previous experimental studies suggest that the endogenous opioid peptides change dopaminergic and serotoninergic tones at the hypothalamic level. We have investigated whether the stimulatory effect of naloxone on luteinizing hormone (LH) secretion is due to its influence on these neurotransmitters. Two experimental models were studied, and two sets of effects on LH secretion induced by intravenous naloxone infusion (20 mg over 2 hours) in 14 normal men 20 to 25 years of age were evaluated: the effect of oral sulpiride (150 mg), a potent dopaminergic antagonist, and the effect of oral fenfluramine (60 mg), a drug that stimulates the serotoninergic receptors by releasing serotonin and inhibiting its reuptake. The study demonstrated that naloxone infusion significantly stimulated the LH secretion throughout the period of observation (P less than 0.01 versus saline). The pretreatment with sulpiride did not change the LH response to naloxone. After fenfluramine pretreatment, naloxone failed to induce any rise in LH secretion. Follicle-stimulating hormone did not show any important variation in either test. The data suggest that in man the stimulatory ability of the opiate receptor antagonist naloxone to elicit a rise in LH plasma levels may involve the serotoninergic, but not the dopaminergic, hypothalamic system. This hypothesis, however, does not exclude the involvement of other hypothalamic neurotransmitters.

The influence of gonadal steroids on the dopamine inhibitory effect on gonadotropin release in men.

The aim of this study was to ascertain whether an interrelationship exists between gonadal steroids and the inhibition of gonadotropin secretion by dopamine. The effect of dopamine infusion (4 micrograms/kg/minute intravenously) on gonadotropin plasma levels in four castrated men (18 to 23 years of age) and in four age-matched normal men was studied. Normal subjects were studied before and after treatment with a specific nonsteroidal estrogen receptor antagonist, CC. LH plasma levels in normal subjects receiving CC had a maximum decrease percentage and a net decrease significantly greater (P less than 0.005 and P less than 0.012, respectively) than those before CC treatment. In castrated subjects the maximum decrease percentage was significantly greater (P less than 0.005) than in control subjects, but it did not show any difference from that of normal subjects receiving CC. In none of the group were significant changes in FSH concentration observed. The findings suggest that whenever there is a gonadal steroid deficiency, dopamine infusion causes an increased sensitivity to LH inhibition. This may be due to a lower endogenous dopaminergic influence on LH secretion.

Dopamine is not involved in the opioid control of luteinizing hormone secretion in man.

The aim of this study was to examine the role of the central dopaminergic system in the mechanisms by which opioid peptides exert their influence on luteinizing hormone (LH) secretion in man. The effects of sulpiride and naloxone on the changes in LH secretion induced by a metenkephalin analog (D-Ala2-MePhe4-Met-(o)-ol-Enkephalin, FK 33824, Sandoz, Basel, Switzerland) (DAMME) and dopamine infusion in four castrated men (21 to 25 years of age) were studied. In these patients, sulpiride pretreatment counteracted the inhibitory effect of dopamine but did not alter the fall of LH plasma levels that DAMME induced. Moreover, in these subjects naloxone reduced the inhibitory effects induced by DAMME but did not change the inhibitory effect of dopamine on LH secretion. These findings confirm that central dopaminergic and opiatergic systems play a role in the control of LH secretion; the data also exclude any interaction between these systems in regulating LH secretion.

Possible significance of transferrin levels in seminal plasma of fertile and infertile men.

Human seminal plasma contains large amounts of transferrin, which is a protein secreted mostly by Sertoli cells. It has been suggested that the concentration of transferrin may serve as a possible clinical marker of Sertoli cell function. Therefore the concentration of this protein in human seminal plasma from fertile and infertile men has been evaluated in order to find a relationship between transferrin concentrations and human semen parameters and plasma FSH levels. Findings show that seminal transferrin in subjects with oligozoospermia or azoospermia is significantly lower than in controls, and that it is strongly related to sperm count. Results also indicate that transferrin secretion can be impaired when plasma FSH levels are still normal, suggesting that seminal transferrin is an early and specific marker of Sertoli cell function. These results, however, do not clarify whether impairment of transferrin secretion by Sertoli cells is due to an organic dysfunction or to an organic secretory alteration.

MRI in insulinomas: preliminary findings.

After establishing the diagnosis of an insulinoma, most surgeons prefer preoperative localization. Selective arteriography is usually considered the gold standard for this purpose. Recently, computed tomography (CT) and preoperative US have contended the role to angiography. MRI has been used in few cases of endocrine pancreatic tumors, and its role in this particular field has to be defined. Between November 1988 and September 1990 we evaluated 7 adult patients who had had surgery in our Surgical Department. Eight tumors were resected in 6 patients who were cured; in an 18-year-old woman surgical treatment was unsuccessful. Arteriography, CT, preoperative US, MRI and intraoperative US detected 2, 6, 6, 5 and 6 tumors, respectively. Two insulinomas (0.2 and 0.7 cm) were found at histologic examination in resected specimen. The ability of intraoperative US and careful surgical exploration to resolve more than 90% of cases makes the preoperative use of arteriography and CT of questionable value. If further experience confirms these findings, US and MRI may suffice.

[The nature of internal medicine]. / La natura della medicina interna.

We investigate here the problem of the nature of Internal Medicine in the context of the different medical disciplines. After reviewing the origins of Internal Medicine and the changes it has undergone since the early 19th century, we deal with the present crisis of this medical branch and the reasons for it. In Italy, the crisis of Internal Medicine began at the dawn of this century when Neurology became a distinct discipline, isolated from the rest of Clinical Medicine. The present-day crisis is determined by the fact that the different constituent parts of Special Medical Pathology have become autonomous specialist disciplines: this situation has convinced some specialists that Internal Medicine, as a single branch, no longer exists. We thus examine the "justification" for the existence of Internal Medicine. Specialist disciplines were originally created to permit deeper analysis of pathological phenomena; however, the great emphasis on detailed and precise analysis of the different phenomena has paved the way for immense progress in pathophysiology and diagnosis, while the synthetic approach fundamental to Clinical Medicine has been neglected. After referring to Claude Bernard's idea that an organism is greater than the sum of its parts, we note that nowadays considerable importance is given to the "whole", that is, to the global study of very complex systems. We thus examine the thesis of Internal Medicine (which views the organism as a whole) as the specific clinical tool enabling the physician to evaluate each single pathophysiological phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

[Analysis of sperm aneuploidy in infertile subjects after chemotherapy treatment]. / Analisi delle aneuploidie spermatiche in soggetti infertili chemiotrattati.

The continuing search for a cure for cancer has developed more aggressive therapies that may damage germ cells, leading to clinical disease in offspring of survivors. Standard therapy for the majority of cancer today consists in combinations of high doses of radiation and chemotherapy drugs. We investigated the effect of cancer treatments on the reproductive potential of men. Multicolor fluorescence in situ hybridization has been used to recognize chromosomes X, Y and 8 in sperm of 10 severely oligozoospermic subjects (sperm concentration < 5,000,000/mL) treated for cancer at least 5 years before the beginning of this study. As controls, we analyzed sperm aneuploidies in 20 fertile men (sperm concentration > 20,000,000/mL) and in 20 severe idiopathic oligozoospermic subjects (sperm concentration < 5,000,000/mL). In all subjects, X- and Y-bearing spermatozoa were present in a normal 1:1 ratio; nevertheless the frequency of 24,XY, 24,XX and 24,YY disomic sperm was significantly higher in patients treated for cancer and in idiopathic oligozoospermic subjects with respect to normozoospermic men. These results suggest that the increase in sperm aneuploidies in treated patients cannot be reported directly to precedent chemotherapy, but reflects the alteration of testicular structure, as in the case of severe idiopathic oligozoospermic subjects. With the advent of intra-cytoplasmic sperm injection, it is possible to offer the opportunity to conceive in men affected by severe oligozoospermia but it is also possible, when the spermatozoa of these subjects are used, to pass sex chromosome abnormalities on to the children. We therefore suggest caution before application of an artificial reproductive technique in severe oligozoospermic patients.

[Microdeletions of the Y chromosome in cryptorchidism and in idiopathic male infertility]. / Microdelezioni del cromosoma Y nel criptorchidismo e nell'infertilità maschile idiopatica.

We investigated the possible role of Y chromosome microdeletions in regions previously shown to be important for male germ cell development in unilateral ex-cryptorchid subjects manifesting important bilateral testiculopathy, in order to clarify whether cryptorchidism could be the expression of an intrinsic congenital testicular abnormality. Microdeletion analysis of the Y chromosome long arm was performed by polymerase chain reaction and confirmed by Southern blot in 40 selected unilateral ex-cryptorchid patients with azoospermia or severe oligozoospermia sustained by severe bilateral testiculopathy (Sertoli cell-only syndrome and severe hypospermatogenesis, respectively), 20 unilateral ex-cryptorchid men with moderate oligozoospermia and normal function of the descended testis, 110 patients affected by severe idiopathic primary testiculopathies, 20 patients affected by moderate idiopathic testiculopathy and, as controls, 50 patients affected by known causes of testiculopathy and 50 fertile controls. Eleven out of the 40 (27.5%) unilateral ex-cryptorchid patients affected by bilateral testiculopathy and 28 out of 110 (25.4%) patients affected by severe idiopathic primary testiculopathy showed microdeletions in the Y chromosome long arm, while all other subjects were normal. Male relatives of patients with deletions were also normal. Microdeletions were distributed in different regions of the Y chromosome long arm, including known regions involved in spermatogenesis (DAZ and RBM genes, AZFa, b and c regions) and other still poorly defined loci. No difference in localization of deletions was evident between ex-cryptorchid and idiopathic patients. Microdeletions in the Y chromosome may be responsible for bilateral severe testicular damage: the clinical consequence, other than idiopathic azoospermia and severe oligozoospermia, may also be unilateral cryptorchidism, probably due to altered testicular responses to mechanisms regulating testicular descent.

[Microdeletion of chromosome Y in male infertility: role of the DAZ gene]. / Microdelezioni del cromosoma Y nell'infertilità maschile: ruolo del gene DAZ.

Microdeletions of the Y chromosome represent the most frequent cause of male infertility, being responsible for 10-15% of cases of azoospermia or severe oligozoospermia. Such mutations localize in one or more loci named azoospermia factor (AZF) a, b and c. Mutations more frequently involve the DAZ gene in AZFc, and could determine both azoospermia and severe oligozoospermia. It is therefore difficult to find a clear relationship between genotype and phenotype. DAZ is present in multiple copies in AZFc, and this causes the gene to be difficult to analyze. In fact, polymerase chain reaction, the principal technique utilized for detection of the deletions, cannot distinguish among the different copies of the gene. Furthermore, it is not clear if all the DAZ copies are expressed in the testis, and other genes, such as CDY1, map in AZFc; therefore their alteration may play a role in determining the phenotype. In this review we report the current knowledge on the function of the Y chromosome in human spermatogenesis. In particular we analyze some of our experimental studies on the role of the DAZ gene family. Expression studies allowed us to clarify that an altered expression of DAZ might cause infertility in patients with severe testiculopathies. Furthermore, we describe for the first time a deletion not involving all the DAZ copies in a patient with severe hypospermatogenesis and we clarify that CDY1 is not involved in the testicular damage observed in patients with deletions of DAZ. These studies elucidate the role of DAZ and have important clinical consequences in the diagnostic and therapeutic approach of the infertile patient, above all when he is a candidate for assisted reproduction techniques, due to the possibility of transmitting the genetic alteration to the offspring.